The epidemiology of mastitis in Australian dairy cattle : a dissertation submitted in partial fulfilment of the requirements for the degree of Masters of Veterinary Studies (Epidemiology)

This study represents an aggregation of knowledge on mastitis within the Australian dairy industry. Aspects of the epidemiology and economics of mastitis have been collated and areas of missing knowledge identified. A clinical treatment trial was conducted on subclinical mastitis to identify the role of therapy upon subclinical infection. The effect of individual variables on mastitis risk was studied and aggregated in order to facilitate the development of a computer simulation model of mastitis within Australian dairy herds. A literature review of mastitis within the Australian dairy industry was conducted. The economic impact of mastitis was examined and the pathway of economic loss to the dairy industry is discussed. The epidemiology of mastitis was studied with special emphasis on quantification of the effect of individual risk factors on the occurrence of disease. Performance parameters for the current diagnostic tests applied within the dairy industry are presented and their suitability for use in a commercial environment discussed. The impact of self-cure and the efficacy of therapeutic intervention in the disease are examined. The role of culling is presented. The chapter concludes with an estimation of die total economic losses experienced on a commercial dairy farm in Victoria in 1998 for three different mastitis levels. The economic benefit to be gained from a reduction in mastitis is also presented. A clinical treatment trial of subclinically infected cows (high somatic cell count) was conducted in order to determine if therapeutic intervention was an effective management tool. Cows with somatic cell counts in excess of 500,000 cells per ml and more than 14 days calved were selected and randomly assigned to treatment and control groups. A pooled quarter milk sample was taken prior to treatment and repeated at around six weeks after treatment. Treated cows received a course of intramammary and parenteral antibiotics and control cows were untreated. Cows were followed for the rest of the lactation of treatment and into the subsequent lactation and somatic cell counts were recorded. The major pathogens identified were S anreus and S uberis. Treatment did not have a significant or commercially useful effect upon bacteriological cure rates, survival of cows to the next lactation or somatic cell count for the remainder of the lactation. Treatment of high somatic cell count cows during lactation is not recommended and is discussed. A requirement exists for the development of a stochastic simulation model of mastitis within Australian dairy herds. The structure of such a model was developed and is presented. Underlying production and somatic cell count responses in Australian cattle were derived. Infection status variables were included and stochasticity was introduced through the use of control variates. State transition probabilities were collected from the literature. Deficiencies in knowledge were identified and methods for modeling these deficient areas discussed. The aggregated information is presented. It is expected that a working stochastic simulation model of mastitis within Australian dairy herds will be developed from infomation collected in this dissertation

The development of a syndromic surveillance system for the extensive beef cattle producing regions of Australia

All surveillance systems are based on an effective general surveillance system because this is the system that detects emerging diseases and the re-introduction of disease to a previously disease free area. General surveillance requires comprehensive coverage of the population through an extensive network of relationships between animal producers and observers and surveillance system officers. This system is under increasing threat in Australia (and many other countries) due to the increased biomass, animal movements, rate of disease emergence, and the decline in resource allocation for surveillance activities. The Australian surveillance system is state-based and has a complex management structure that includes State and Commonwealth government representatives, industry stakeholders (such as producer bodies) and private organisations. A developing problem is the decline in the effectiveness of the general surveillance system in the extensive (remote) cattle producing regions of northern Australia. The complex organisational structure of surveillance in Australia contributes to this, and is complicated by the incomplete capture of data (as demonstrated by slow uptake of electronic individual animal identification systems), poorly developed and integrated national animal health information systems, and declining funding streams for field and laboratory personnel and infrastructure. Of major concern is the reduction in contact between animal observers and surveillance personnel arising from the decline in resource allocation for surveillance. Fewer veterinarians are working in remote areas, fewer producers use veterinarians, and, as a result, fewer sick animals are being investigated by the general surveillance system. A syndrome is a collection of signs that occur in a sick individual. Syndromic surveillance is an emerging approach to monitoring populations for change in disease levels and is based on statistical monitoring of the distribution of signs, syndromes and associations between health variables in a population. Often, diseases will have syndromes that are characteristic and the monitoring of these syndromes may provide for early detection of outbreaks. Because the process uses general signs, this method may support the existing (struggling) general surveillance system for the extensive cattle producing regions of northern Australia. Syndromic surveillance systems offer many potential advantages. First, the signs that are monitored can be general and include any health-related variable. This generality provides potential as a detector of emerging diseases. Second, many of the data types used occur early in a disease process and therefore efficient syndromic surveillance systems can detect disease events in a timely manner. There are many hurdles to the successful deployment of a syndromic surveillance system and most relate to data. An effective system will ideally obtain data from multiple sources, all data will conform to a standard (therefore each data source can be validly combined), data coverage will be extensive (across the population) and data capture will be in real time (allowing early detection). This picture is one of a functional electronic data world and unfortunately this is not the norm for either human or animal heath. Less than optimal data, lack of data standards, incomplete coverage of the population and delayed data transmission result in a loss of sensitivity, specificity and timeliness of detection. In human syndromic surveillance, most focus has been placed on earlier detection of mass bioterrorism events and this has concentrated research on the problems of electronic data. Given the current state of animal health data, the development of efficient detection algorithms represents the least of the hurdles. However, the world is moving towards increased automation and therefore the problems with current data can be expected to be resolved in the next decade. Despite the lack of large scale deployment of these systems, the question is becoming when, not whether these system will contribute. The observations of a stock worker are always the start of the surveillance pathway in animal health. Traditionally this required the worker to contact a veterinarian who would investigate unusual cases with the pathway ending in laboratory samples and specific diagnostic tests. The process is inefficient as only a fraction of cases observed by stock workers end in diagnostic samples. These observations themselves are most likely to be amenable to capture and monitoring using syndromic surveillance techniques. A pilot study of stock workers in the extensive cattle producing Lower Gulf region of Queensland demonstrated that experienced non-veterinary observers of cattle can describe the signs that they see in sick cattle in an effective manner. Lay observers do not posses a veterinary vocabulary, but the provision of a system to facilitate effective description of signs resulted in effective and standardised description of disease. However, most producers did not see personal benefit from providing this information and worried that they might be exposing themselves to regulatory impost if they described suspicious signs. Therefore the pilot study encouraged the development of a syndromic surveillance system that provides a vocabulary (a template) for lay observers to describe disease and a reason for them to contribute their data. The most important disease related drivers for producers relate to what impact the disease may have in their herd. For this reason, the Bovine Syndromic Surveillance System (BOSSS) was developed incorporating the Bayesian cattle disease diagnostic program BOVID. This allowed the observer to receive immediate information from interpretation of their observation providing a differential list of diseases, a list of questions that may help further differentiate cause, access to information and other expertise, and opportunity to benchmark disease performance. BOSSS was developed as a web-based reporting system and used a novel graphical user interface that interlinked with an interrogation module to enable lay observers to accurately and fully describe disease. BOSSS used a hierarchical reporting system that linked individual users with other users along natural reporting pathways and this encouraged the seamless and rapid transmission of information between users while respecting confidentiality. The system was made available for testing at the state level in early 2006, and recruitment of producers is proceeding. There is a dearth of performance data from operational syndromic surveillance systems. This is due, in part, to the short period that these systems have been operational and the lack of major human health outbreaks in areas with operational systems. The likely performance of a syndromic surveillance system is difficult to theorise. Outbreaks vary in size and distribution, and quality of outbreak data capture is not constant. The combined effect of a lack of track record and the many permutations of outbreak and data characteristics make computer simulation the most suitable method to evaluate likely performance. A stochastic simulation model of disease spread and disease reporting by lay observers throughout a grid of farms was modelled. The reporting characteristics of lay observers were extrapolated from the pilot study and theoretical disease was modelled (as a representation of newly emergent disease). All diseases were described by their baseline prevalence and by conditional sign probabilities (obtained from BOVID and from a survey of veterinarians in Queensland). The theoretical disease conditional sign probabilities were defined by the user. Their spread through the grid of farms followed Susceptible-Infected-Removed (SIR) principles (in herd) and by mass action between herds. Reporting of disease events and signs in events was modelled as a probabilistic event using sampling from distributions. A non-descript disease characterised by gastrointestinal signs and a visually spectacular disease characterised by neurological signs were modelled, each over three outbreak scenarios (least, moderately and most contagious). Reports were examined using two algorithms. These were the cumulative sum (CuSum) technique of adding excess of cases (above a maximum limit) for individual signs and the generic detector What’s Strange About Recent Events (WSARE) that identifies change to variable counts or variable combination counts between time periods. Both algorithms detected disease for all disease and outbreak characteristics combinations. WSARE was the most efficient algorithm, detecting disease on average earlier than CuSum. Both algorithms had high sensitivity and excellent specificity. The timeliness of detection was satisfactory for the insidious gastrointestinal disease (approximately 24 months after introduction), but not sufficient for the visually spectacular neurological disease (approximately 20 months) as the traditional surveillance system can be expected to detect visually spectacular diseases in reasonable time. Detection efficiency was not influenced greatly by the proportion of producers that report or by the proportion of cases or the number of signs per case that are reported. The modelling process demonstrated that a syndromic surveillance system in this remote region is likely to be a useful addition to the existing system. Improvements that are planned include development of a hand-held computer version and enhanced disease and syndrome mapping capability. The increased use of electronic recording systems, including livestock identification, will facilitate the deployment of BOSSS. Long term sustainability will require that producers receive sufficient reward from BOSSS to continue to provide reports over time. This question can only be answered by field deployment and this work is currently proceeding

The development of a syndromic surveillance system for the extensive beef cattle producing regions of Australia

All surveillance systems are based on an effective general surveillance system because this is the system that detects emerging diseases and the re-introduction of disease to a previously disease free area. General surveillance requires comprehensive coverage of the population through an extensive network of relationships between animal producers and observers and surveillance system officers. This system is under increasing threat in Australia (and many other countries) due to the increased biomass, animal movements, rate of disease emergence, and the decline in resource allocation for surveillance activities. The Australian surveillance system is state-based and has a complex management structure that includes State and Commonwealth government representatives, industry stakeholders (such as producer bodies) and private organisations. A developing problem is the decline in the effectiveness of the general surveillance system in the extensive (remote) cattle producing regions of northern Australia. The complex organisational structure of surveillance in Australia contributes to this, and is complicated by the incomplete capture of data (as demonstrated by slow uptake of electronic individual animal identification systems), poorly developed and integrated national animal health information systems, and declining funding streams for field and laboratory personnel and infrastructure. Of major concern is the reduction in contact between animal observers and surveillance personnel arising from the decline in resource allocation for surveillance. Fewer veterinarians are working in remote areas, fewer producers use veterinarians, and, as a result, fewer sick animals are being investigated by the general surveillance system. A syndrome is a collection of signs that occur in a sick individual. Syndromic surveillance is an emerging approach to monitoring populations for change in disease levels and is based on statistical monitoring of the distribution of signs, syndromes and associations between health variables in a population. Often, diseases will have syndromes that are characteristic and the monitoring of these syndromes may provide for early detection of outbreaks. Because the process uses general signs, this method may support the existing (struggling) general surveillance system for the extensive cattle producing regions of northern Australia. Syndromic surveillance systems offer many potential advantages. First, the signs that are monitored can be general and include any health-related variable. This generality provides potential as a detector of emerging diseases. Second, many of the data types used occur early in a disease process and therefore efficient syndromic surveillance systems can detect disease events in a timely manner. There are many hurdles to the successful deployment of a syndromic surveillance system and most relate to data. An effective system will ideally obtain data from multiple sources, all data will conform to a standard (therefore each data source can be validly combined), data coverage will be extensive (across the population) and data capture will be in real time (allowing early detection). This picture is one of a functional electronic data world and unfortunately this is not the norm for either human or animal heath. Less than optimal data, lack of data standards, incomplete coverage of the population and delayed data transmission result in a loss of sensitivity, specificity and timeliness of detection. In human syndromic surveillance, most focus has been placed on earlier detection of mass bioterrorism events and this has concentrated research on the problems of electronic data. Given the current state of animal health data, the development of efficient detection algorithms represents the least of the hurdles. However, the world is moving towards increased automation and therefore the problems with current data can be expected to be resolved in the next decade. Despite the lack of large scale deployment of these systems, the question is becoming when, not whether these system will contribute. The observations of a stock worker are always the start of the surveillance pathway in animal health. Traditionally this required the worker to contact a veterinarian who would investigate unusual cases with the pathway ending in laboratory samples and specific diagnostic tests. The process is inefficient as only a fraction of cases observed by stock workers end in diagnostic samples. These observations themselves are most likely to be amenable to capture and monitoring using syndromic surveillance techniques. A pilot study of stock workers in the extensive cattle producing Lower Gulf region of Queensland demonstrated that experienced non-veterinary observers of cattle can describe the signs that they see in sick cattle in an effective manner. Lay observers do not posses a veterinary vocabulary, but the provision of a system to facilitate effective description of signs resulted in effective and standardised description of disease. However, most producers did not see personal benefit from providing this information and worried that they might be exposing themselves to regulatory impost if they described suspicious signs. Therefore the pilot study encouraged the development of a syndromic surveillance system that provides a vocabulary (a template) for lay observers to describe disease and a reason for them to contribute their data. The most important disease related drivers for producers relate to what impact the disease may have in their herd. For this reason, the Bovine Syndromic Surveillance System (BOSSS) was developed incorporating the Bayesian cattle disease diagnostic program BOVID. This allowed the observer to receive immediate information from interpretation of their observation providing a differential list of diseases, a list of questions that may help further differentiate cause, access to information and other expertise, and opportunity to benchmark disease performance. BOSSS was developed as a web-based reporting system and used a novel graphical user interface that interlinked with an interrogation module to enable lay observers to accurately and fully describe disease. BOSSS used a hierarchical reporting system that linked individual users with other users along natural reporting pathways and this encouraged the seamless and rapid transmission of information between users while respecting confidentiality. The system was made available for testing at the state level in early 2006, and recruitment of producers is proceeding. There is a dearth of performance data from operational syndromic surveillance systems. This is due, in part, to the short period that these systems have been operational and the lack of major human health outbreaks in areas with operational systems. The likely performance of a syndromic surveillance system is difficult to theorise. Outbreaks vary in size and distribution, and quality of outbreak data capture is not constant. The combined effect of a lack of track record and the many permutations of outbreak and data characteristics make computer simulation the most suitable method to evaluate likely performance. A stochastic simulation model of disease spread and disease reporting by lay observers throughout a grid of farms was modelled. The reporting characteristics of lay observers were extrapolated from the pilot study and theoretical disease was modelled (as a representation of newly emergent disease). All diseases were described by their baseline prevalence and by conditional sign probabilities (obtained from BOVID and from a survey of veterinarians in Queensland). The theoretical disease conditional sign probabilities were defined by the user. Their spread through the grid of farms followed Susceptible-Infected-Removed (SIR) principles (in herd) and by mass action between herds. Reporting of disease events and signs in events was modelled as a probabilistic event using sampling from distributions. A non-descript disease characterised by gastrointestinal signs and a visually spectacular disease characterised by neurological signs were modelled, each over three outbreak scenarios (least, moderately and most contagious). Reports were examined using two algorithms. These were the cumulative sum (CuSum) technique of adding excess of cases (above a maximum limit) for individual signs and the generic detector What’s Strange About Recent Events (WSARE) that identifies change to variable counts or variable combination counts between time periods. Both algorithms detected disease for all disease and outbreak characteristics combinations. WSARE was the most efficient algorithm, detecting disease on average earlier than CuSum. Both algorithms had high sensitivity and excellent specificity. The timeliness of detection was satisfactory for the insidious gastrointestinal disease (approximately 24 months after introduction), but not sufficient for the visually spectacular neurological disease (approximately 20 months) as the traditional surveillance system can be expected to detect visually spectacular diseases in reasonable time. Detection efficiency was not influenced greatly by the proportion of producers that report or by the proportion of cases or the number of signs per case that are reported. The modelling process demonstrated that a syndromic surveillance system in this remote region is likely to be a useful addition to the existing system. Improvements that are planned include development of a hand-held computer version and enhanced disease and syndrome mapping capability. The increased use of electronic recording systems, including livestock identification, will facilitate the deployment of BOSSS. Long term sustainability will require that producers receive sufficient reward from BOSSS to continue to provide reports over time. This question can only be answered by field deployment and this work is currently proceeding

Dispersion measurement of microstructured negative curvature hollow core fiber

We present measurements of the dispersion of two negative curvature fibers at and around 1  μm. These fibers are suitable for beam delivery of both high power and ultrashort pulse lasers with one designed to operate at 1030 nm and the other designed for dual wavelength delivery at 515 and 1030 nm. Both fibers were found to exhibit anomalous dispersion measured to be 2.17±0.25  ps nm−1 km−1for the fundamental mode rising to 4.69±0.17  ps nm−1 km−1 for the first-order mode in the 1030-nm fiber. Dispersion in the double wavelength fiber was found to be higher at 3.81±0.03  ps nm−1 km−1 for the fundamental mode guiding at 1030 nm

Global MicroRNA Profiling of the Mouse Ventricles during Development of Severe Hypertrophic Cardiomyopathy and Heart Failure

<div><p>MicroRNAs (miRNAs) regulate post-transcriptional gene expression during development and disease. We have determined the miRNA expression levels of early- and end-stage hypertrophic cardiomyopathy (HCM) in a severe, transgenic mouse model of the disease. Five miRNAs were differentially expressed at an early stage of HCM development. Time-course analysis revealed that decreased expression of miR-1 and miR-133a commences at a pre-disease stage, and precedes upregulation of target genes causal of cardiac hypertrophy and extracellular matrix remodelling, suggesting a role for miR-1 and miR-133a in early disease development. At end-stage HCM, 16 miRNA are dysregulated to form an expression profile resembling that of other forms of cardiac hypertrophy, suggesting common responses. Analysis of the mRNA transcriptome revealed that miRNAs potentially target 15.7% upregulated and 4.8% downregulated mRNAs at end-stage HCM, and regulate mRNAs associated with cardiac hypertrophy and electrophysiology, calcium signalling, fibrosis, and the TGF-β signalling pathway. Collectively, these results define the miRNA expression signatures during development and progression of severe HCM and highlight critical miRNA regulated gene networks that are involved in disease pathogenesis.</p> </div

RT-qPCR validation of changes in mRNA expression levels.

<p>Extended time course analysis of mRNA expression levels. Fold change is shown compared to NTG mice age 5 days. *P<0.05.</p

Validated miRNAs differentially expressed in DBL mice.

<p>MicroRNAs significantly upregulated (top panel) or downregulated (bottom panel) (<i>P</i><0.05).</p

Potential impact of miRNA regulation on mRNA transcript levels.

<p>mRNAs upregulated (left) and downregulated (right) during late-stage HCM are represented. Proportion of mRNAs with conserved target sites for conversely expressed miRNAs is shown in black.</p